BIOS E-162B Human Pathophysiology

Harvard Extension School

NEUROPATHOPHYSIOLOGY I
Synaptic transmission and what can go wrong

Nancy Long Sieber, Ph.D.

September 17, 2012

I. SynapticTransmission

A. Nervesignalstravelfromoneneurontoanother,orfromaneurontosomeotherexcitable
tissue,suchasmuscleorglandulartissueatsynapses.
1. Insomecases,theelectricsignaltravelsdirectlyfromonecelltoanotheratsites
wherethecytoplasmsoftwocellsareindirectcontactwitheachother.Thesesites
arecalledgapjunctions,andareespeciallyimportantincardiacandsmoothmuscle.
2. Mostmammaliansynapsesarechemicalsynapses.Chemicalsynapses:
a. Allowforonewaytransmissionofnervesignals.
b. Areasiteofintegrationofinhibitoryandexcitatoryinput.
c. Areaccessibletodrugsandtoxins.
3. Sequenceofeventsinsynaptictransmission:
a. Anactionpotentialreachestheaxonterminalofoneneuron(thepresynaptic
neuron).
i. Thiscausestheopeningofvoltagegatedcalciumchannelsinthe
membraneofthepresynapticneuron.
ii. Calciumdiffusesintotheaxonterminal,causingvesiclescontaining
neurotransmittertofusewiththeplasmamembrane.Thecontentsofthe
vesiclesarereleasedbyexocytosis.
b. Theneurotransmitterdiffusesacrossanarrowregioncalledthesynapticcleft(10
20nanometer(=109meter)),andthenbindstoreceptorsonthepostsynapticcell
membrane.
c. Thesereceptorsareassociatedwithligandgatedionchannels,andtheopeningof
thesechannelsgivesrisetoagradedpotentialcalledthepostsynapticpotential.
i. IfthereceptorisassociatedwithaNa+channel,thebindingof
neurotransmittercausesthemembranetobecomedepolarized.Thisgivesrise
toanexcitatorypostsynapticpotential(EPSP).
ii. IfthereceptorisassociatedwithaK+channel,thebindingof
neurotransmittercausesthemembranetobecomehyperpolarized.The
resultingchangeinmembranepotentialiscalledaninhibitorypostsynaptic
potential(IPSP).
d. Thesepostsynapticpotentialscanundergospatialandtemporalsummation.
i. Potentialsgeneratedinadjacentareascauseareadditive,andcausea
largerchangeinmembranepotentialthaneitherpotentialalone(spatial
summation).

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 ii. Ifasecondpotentialoccursbeforethefirsthasdiedaway,theresulting
changeinmembranepotentialislarger(temporalsummation).
e. Iftheregionbetweenthecellbodyandtheaxonknownastheinitialsegment(or
axonhillock)isdepolarizedtothresholdbythebalanceoftheEPSPsandIPSPs,
thenanactionpotentialwillbeinitiated.Thetimedelayatanexcitatorysynapse
isabout0.5milliseconds
f. Terminationofsynaptictransmission
i. Neurotransmittersareindynamicequilibriumwiththeirreceptors,binding
andunbinding.
ii. Unboundneurotransmittermaybe
Takenupbythepresynapticneuron(eg:norepinephrine,serotonin)
Inactivatedbyenzymes(eg:acetylcholine)
iii. Thedurationofneurotransmitteravailabilityisontheorderof1020
millisec.

B. Drugstotreatdisordersofthenervoussystemoftenacttochangesomeaspectof
synaptictransmission.
1. Someincreaseordecreasetheamountofneurotransmitterreleased.
a. Somedrugschangethethresholdforactionpotentialfiringinthepresynaptic
neuron.
b. Othersinterferewiththepackagingofneurotransmitterintopresynapticvesicles,
resultinginthereleaseoflessneurotransmitter.
2. Someactbybindingtothereceptor
a. Notethatthesameneurotransmittermaybindtomorethanonetypeofreceptor,
anddifferentreceptors,dependingonwheretheyrelocated,canhavedifferent
effectsonthebrain.Drugscanbedesignedtobindpreferentiallytoaparticular
subclassofreceptors,allowingforfinetuningoftheneuralresponse.
b. drugsthatbindtoandactivateareceptor(i.e.actliketheendogenous
neurotransmitter)arecalledagonists.
c. drugsthatbindtoandinactivatethereceptor(i.e.blocktheactionofthe
endogenousneurotransmitter)arecalledantagonists.
3. Othersincreaseordecreasetheactivityofenzymesthatdegradetheneurotransmitter,
orbyincreasingordecreasingtheuptakeofneurotransmitterbypresynapticneurons.

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Understanding synaptic transmission can help us to understand certain aspects of mental illness.
While mood disorders, such as major depression and schizophrenia are undoubtedly brought
about by many different factors, abnormalities in levels of certain neurotransmitters is thought to
contribute to these conditions. A major theory of mood disorders is the monoamine hypothesis,
which states that imbalances in certain monoamine neurotransmitters, including norepinephrine
(NE), serotonin and dopamine give rise to the symptoms of these diseases. Much of what we
know about the roles of these neurotransmitters in these diseases comes from the use of
pharmacologic agents. However, as well see, this theory is not sufficient to completely explain
these conditions.

II. Majordepressionisacomplexconditionthatlikelyinvolvesinteractionsbetween
genesandtheenvironment.

A. Majordepressionischaracterizedbyextremeanddebilitatingsadnessthattypically
developsintheabsenceofanyobviousexogenouscause.
1. Itisthoughtthatmorethan15%ofAmericansareaffectedbymajordepressionat
somepointintheirlives.
2. Asof2005,about10%ofAmericansovertheageof6wereusingantidepressant
drugs,upfrom5%in1996.

B. Thedepressivesyndromeischaracterizedbylonglastingdepressedmood,feelingsof
guilt,anxiety,andrecurrentthoughtsofdeathandsuicide.
1. About85%ofpeoplewhohavebeendiagnosedwithdepressionalsosufferfroma
generalizedanxietydisorder,and35%havesymptomsofapanicdisorder.
2. Whilethesymptomsofdepressionandanxietyarequitedifferent(atthelowpointof
depressionnotmuchmatters,whileapersoninthegripofananxietyattackmay
experiencefear,panicoranxietyinacompletelybenignsituation),bothoftenrespond
tothesametypesofdrugsandpsychotherapy.

C. Theinvolvementofmonoaminesindepressionwasfirsthintedatbydrugsdevelopedin
the1950s.
1. Reserpine,adrugdevelopedtotreathypertension,triggereddepressioninabout15%
ofpatientswhousedit.Itwaslatershowntocausedepletionofmonoaminesby
interferingwiththepackagingoftheseneurotransmittersintovesicles.
2. Iproniazid,adrugdevelopedtotreattuberculosis,elevatedthemoodofmany
depressedpatients.Thisdrugwaslaterfoundtoinhibittheenzymethatbreaksdown
monoamines.

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D. Furtherstudiesshowedthatdepressedpatientshadlowerlevelofmetabolitesofthese
monoaminesintheircerebrospinalfluid.

E. Brainsamplescollectedfromdeceaseddepressedpatientsshowedhighernumbersof
receptorsfortheseneurotransmitters.Thisincreasereflectsupregulationofreceptors,a
commonresponsetodepletionofasignalingmolecule.

F. Theearliestantidepressantdrugsactinageneralwaytoincreaseavailabilityof
monoaminesatthesynapse.
1. Someblockmonoamineoxidase(MAO),anenzymefoundinsidethepresynaptic
neuron,aswellasinthesynapticcleft,thatnormallylimitstheavailabilityof
monoamines.
a. Theneteffectofmonoamineoxidaseinhibitorsishigherlevelsneurotransmitters
inthesynapticcleft,increasingtheireffectonthepostsynapticcell.
b. Thesedrugshaveasideeffectofelevatingbloodpressuretodangerouslevels,
particularlywhenpeopleeatcertainfoods,includingagedcheeseandchocolate.
Asaresult,theyarenotwidelyused.
2. Someselectivelyblockmonoaminereuptakebythepresynapticneuron.

G. Morerecentlydevelopeddrugsfocusspecificallyonserotonin
1. Lackofserotoninseemstocausedepressioninasomewhatindirectmanner.
a. Serotoninisconsideredtobepermissivefortheavailabilityofother
neurotransmitters,includingnorepinephrine.
b. Whenserotoninlevelsfall,norepinephrinesignalingisdampened.
c. Serotoninappearstoaffectothertypesofneuronsaswell,anditsdepletionmay
beresponsibleforothermanifestationsofdepression,including
i. Lossofappetite,libido,andsleep(regulatedbythehypothalamus)
ii. Flatteningofemotionalresponses(regulatedbytheamygdala)
2. Mostdrugsacttoinhibitthereuptakeofserotoninbythepresynapticneuron,andare
calledselectiveserotoninreuptakeinhibitorsorSSRIs.
a. TheseincludeProzac,Zoloft,Praxil,etc..
b. Thespecificityofthesedrugsminimizestheirsideeffects,whichisthemajor
reasonthattheyhavebecomesomewidelyused.
c. Also,sinceserotoninisinvolvedinsomanyaspectsofmoodandbehavior,these
drugscannormalizemanydifferentaspectsofonespersonality.
d. Overthepastfewyears,greaterconcernshavebeenraisedaboutwhetherthese
drugsincreasetheriskofsuicide,particularlyinyoungpeople.
3. Whataboutpsychotherapy?Brainimagingstudiesshowthesamebrainregionsthat
areaffectbydrugsthattreatmentalillnessarealsoaffectedbypsychotherapy
(althoughthemechanismofactionmaybedifferent).Successratesareoftenhigh,
andlastlongerthandrugs.

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 4. FORNEXTYR:Putthismaterialonslides

H. However,itappearsthatthemonoaminehypothesisdescribedaboveisnotsufficientto
fullyexplainmajordepression.
1. Theactionsofantidepressantdrugsthemselvesilluminatethegapsinthis
explanation.
a. Antidepressantdrugsareeffectiveinlessthan50%ofcasesofdepression.They
workbestinpeoplewithseveredepression,orinpeoplewithchronicmild
depression.
b. Antidepressantsmustbeusedforseveralweeksbeforetheireffectsareseenthis
suggestsamorecomplexinteractionbetweenthedrugandthenervoussystem.
Thedrugsmightactdownstreamfromtheneurotransmitterreceptor,by
controllinggeneexpression,forexample.
c. Antidepressantsandmoodstabilizingdrugshavewidespreadsideeffects,
suggestingtheiractionsgobeyondsimplyadjustinglevelsofmonoamines.
2. Geneticpolymorphisms(differentformsofthesamegene)mayexplainwhysome
peoplearemorepronetodepressionthanothers.
a. Forexample,thereare2differentformsofthegenefortheserotonintransporter.
Peoplewiththeshortformofthegenearemorelikelytoexperiencedepression
afteramajorlifestress(eg:jobloss,divorce,etc.).Interestingly,peoplewho
havethegenebutdonotexperienceasignificantlossarenomorelikelytobe
depressedthanpeoplewiththelongerformofthegene.
b. Similarly,childrenwhohaveexperiencedabuseorneglectaremorelikelyto
becomedepressediftheyhavetheshortversionofthegene.
3. Alterationsinparticularbrainregions,particularlythoseinvolvedintheperceptionof
stressandthestressresponsemaycontributetodepression,aswell.
a. Thestressresponse,whichyoullhearmoreaboutsoon,triggersthereleaseof
stresshormonesthataffectcertainbrainregions,includingthehippocampus
(involvedinshorttermmemory)andtheamygdala(involvedinemotional
responses,particularlytofrighteningstimuli).
i. Inexperimentalanimals,stresscanleadtochangesinthehippocampus
thataresimilartowhatisseenindepression.
ii. Thesameserotoningenedescribedaboveappearstomaketheamygdala
hypersensitive.Thisseemstocausethepersontobehypersensitiveto
negativestimuli.Someevidencesuggeststhatthis,inturn,causestheperson
toproducehigherthannormallevelsofstresshormones,whichcantrigger
depression.
b. Anotherbrainregion,theprefrontalcortexmayalsobeinvolved.Theprefrontal
cortex,whichisconsideredtobetheseatofrationalthought,tendstobe
underactiveinpeoplewhoaredepressed.

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 I. Somequestionstoconsider:
1. Isdepressionbroughtonbythestressesofmodernlife?Isthereanythingthatcanbe
donetopreventit?
2. Shoulddepression,particularlyinyoungpeople,alwaysbetreatedwithdrugs?Do
thesedrugsincreasetheriskofsuicide?Ifso,whatabouttheriskofsuicideina
depressedpersonwhoisnottreated?
3. Whatareotherconsequencesofnottreatingdepression?Isdepressionaprogressive
disease?
4. Shouldhealthinsurancecompaniespayforyearsoftalktherapy,whendrugsmay
givethesameresultinashortertime?
5. Howlongshouldpeoplestayonantidepressantdrugs?
6. Whataboutdepressioninothercountries?Howdodifferentculturesthinkabout
mentalhealth?HastheAmericanpharmaceuticalindustryexporteddepression?

III. Bipolardisorder(previouslyknownasmanicdepressivedisorder)ischaracterized
byperiodsofdepressionaswellasequallydisruptiveperiodsofeuphoria.

A. About25%ofpatientswithamajordepressivedisorderalsoexperienceatleastone
manicepisodeatsomepointlaterinlife.
1. Bipolardisorderappearstobedistinctfromunipolardepression.Ittendstostrike
peopleatarelativelyyoungage(aboutage20,vs.30forunipolardepression).
2. Inmostcases,thereisnoobvioustriggerforthedepressiveormanicepisode,andthe
episodesrecurthroughoutlife.

B. Treatment
1. Lithiumisthedrugofchoiceforbipolardisorder.Itactstostabilizelevelsofvarious
neurotransmitters,includingnorepinephrine,serotoninanddopamine.
2. Antidepressantsarealsousedtotreatdepressiveattacks,andantipsychoticsareused
totreatmanicattacks.
3. Anticonvulsantdrugs,whichhavetraditionallybeenusedtotreatepilepsy,havealso
beenfoundtobeeffectiveintreatingbipolardisorder.Thesedrugshelpcontrolthe
sensitivityofneuralmembranestostimulatorysignals.Thereissomethoughtthatan
underlyingmechanismofbipolardisorderisabnormalneuralsensitivity,similarto
whatisseeninepilepsy.

C. Somepsychiatristsbelievethatbipolardisordercanstartmuchearlierinlifeeven
toddlershavebeengiventhisdiagnosis.Thisisacontroversialfield,andtheemerging
consensusisthatbipolarinchildrenisreal,butitisunclearhowcommonitis.Thedrugs
usedtotreatthisdiseasehaveastrongsedativeeffect,whichdoestendtoeliminatethe
disruptivebehaviorofthesechildren,butnotwithoutrisktothechild.

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IV. Dopamineplaysavarietyofrolesinthenervoussystem.

A. Itisinvolvedintheinitiationofmovement,andlevelsthataretoolowinaparticularpartofthe
braingiverisetotherigidityofParkinsonsdisease(whichwellhearaboutnextweek).

B. Levelsthataretoohighcancausehallucinationsandpsychosisassociatedwithschizophrenia.

C. Dopaminealsohelpsregulatemood.
1. Itseemstobecentraltoourfeelingofpleasureandreward,andmanyillicitdrugsacton
dopaminergicpathwaystoactivatethesecircuits.
2. Dopamineisalsoassociatedwithmotivationandmemory.
a. Whenyoudosomethingthatbenefitsyouinabiologicalway,suchaseatingsometasty
food,orfindinganappealingpartner,dopamineisreleased.Thisgivesyouafeelingof
pleasure,whichreinforcesthisbehavior.
b. Whenyoudofindsomethinggoodabushwithripeberries,orastashhiddenof
chocolate,thereleaseofdopaminealsoreinforcesthememoryofwherethegoodstuffis
located.
3. Wehavelearnedagreatdealabouttheroleofdopamineinpersonalityandmoodbystudying
thediseasesanddrugsthataffectdopaminergicneurotransmission.

V. Schizophreniaisassociatedwithanexcessofdopaminergicneurotransmission.(i.e.
neurotransmissionbydopamineproducingneurons).

A. Schizophreniaischaracterizedbydisorganizedthinkingandspeech,delusionsand
hallucinations.Patientsareoftenwithdrawn,andshowflatexpressions.
1. About2millionAmericansareschizophrenic.
2. Ageofonsetisusuallybetween25and35years.

B. Inthe1950s,itwasshownthatdrugsthatdecreasedopaminergicneurotransmission(eg:
thorazine)reducethesymptomsofschizophrenia.Howwouldyoudesignadrugthatwould
decreasedopaminergicneurotransmission?

VI. Recreationaldrugsmanipulatethesameneurotransmittersthatareinvolvedinmood.

A. Amphetamines,especiallycrystalmethamphetaminetriggerthereleaseoflargeamountsof
norepinephrineanddopamine.Someformsofamphetaminealsoincreaseserotoninrelease.
Methamphetaminealsoblocksreuptakeoftheseneurotransmittersbythepresynapticneuron,
andinhibitstheenzymesthatbreakthemdown.
1. Amphetaminesarestimulants.Thereleaseofdopaminestimulatesneuralcircuitsassociated
withfeelingsofpleasure.Norepinephrineincreasesalertnessandpreventsfatigue.Thenet
effectisarushofenergyandeuphoria,whichcanlastforhours.Italsoincreasessexual
desire(butmayinterferewithperformance).Useofthisdrugisassociatedwithunsafe
sexualpractices,andthespreadofHIVandotherSTDs.

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 2. Sideeffectsofthesedrugsincludeincreasedbloodpressureandheartrate.Cardiac
arrhythmiascanoccur,whichcanpotentiallyleadtocardiacarrest.Amphetaminescanalso
causehyperthermiaandconvulsions,whichcanbelethal.
3. Thenwhat?Afteradayorsoofeuphoria,wildphysicalactivity,notsleeping,noteating,
etc.,theneuronsbecomedepletedoftheseneurotransmitters,leavingtheuserfeeling
drained,depressed,irritableanddesperateformore.
4. Ecstasy(MDMA)hasastrongereffectonserotonin,whichcausesamoremellowhighthan
methamphetamine.Ithasmanyofthesamedangeroussideeffects,though.

B. Cocaineactsonthesesamepathways.Itblocksreuptakeofdopamineandnorepinephrine,
keepingthesedrugsinthesynapselonger.Becauseitismetabolizedmorerapidly,thehighfrom
cocaineusuallylasts20to40minutes,comparedtodaysformethamphetamine.Cocainehas
strongeffectsontheheart,andcancausecardiacarrest.

VII. Whatdoesitmeantobeaddictedtosomething?

A. Broadlyspeaking,addictionmeansthatyoucontinuetouseadrug,despiteitsadversehealthand
socialconsequences.
1. Onecommonpathwayforalladdictionsappearstobedopaminereleaseinthemidbrain,
wherethepleasurecenterlies.Theideathatthebrainhasapleasurecentermakessenseit
encouragesustoengageinbehaviorsthatpromoteoursurvivalbothasindividualsandasa
species.
2. Behaviorsthathavethepotentialtobedestructivealsotriggerdopaminerelease.
a. Theseincludeuseofdrugsthatcausedesirablemoodchanges,suchastobacco,alcohol
orcocaine.Italsoincludesbehaviorslikegambling,shoppingandovereating.
b. Ifarewardisconsistentlydelivered,dopaminereleaseeventuallydeclinesthereis
nothingmoretolearnaboutthisstimulus,anditbecomespredictable.
c. However,ifthebehavioroccasionallyfailstodeliverareward,whenyoudogetthe
reward,evenmoredopaminetobereleased.Itisasthoughthebrainisworkinghardto
figureoutthepatternofrewarddelivery.Thisseemstobepartofwhygamblingcanbe
soaddictive.Italsocontributestotheappealoffollowingsportingeventsand
presidentialelections.

B. Physicalvs.psychologicaladdiction
1. Physicaldependenceischaracterizedbydevelopingtolerancetoadrugi.e.,needingmore
andmoretoreachthesamelevelofintoxication,andthepresenceofwithdrawlsymptoms
whenyoudontusethedrug.Eventually,manyaddictsnolongerexperienceanykindof
highwhileusingthedrug,yettheystillfeelcompelledtousethedrug.
2. Psychologicaladdictionincludesthebehavioralpatternsaroundtheuseofthedrug.
a. Thismayberelatedtotheassociationbetweenmemoryanddopaminerelease.
b. Sometimesjusttheritualsassociatedwiththeuseofadrugbringonacravingforitthe
preparationofasyringefullofheroin,associationofhavingacigarette,alongwithacup
ofcoffee,afterameal.

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 c. Thisassociationmakesaddictionsparticularlyhardtobeat.Whenarecoveringaddict
seessomethingthatremindsthemofadrugtheyonceusedasyringe,apipe,oranold
friendtheyonceshareddrugswith,thememorycancreateapowerfulurgetousethe
drugagain.
3. Physicalandpsychologicaladdictionstendtogotogether,butnotalways.Forexample,you
canbecomephysicallyaddictedtopainkillersaftersurgery,butnothaveapsychological
addiction.Youmightalsohaveapsychologicaladdictiontoapatternofdruguse,likea
glassofwineeverynightwithdinner,butnotbetrulyphysicallyaddictedtoit.

C. Behavioraladdictionshavesomeofthesamecharacteristicsasaddictionstodrugs.These
includegambling,shopping,eatingandsexaddictions.

D. Somelikelymechanismsofaddictionrelatebacktohowdrugsactonthesynapse.Recallthat
drugslikecocaineandamphetamineacttotriggerthereleaseoflargeamountsofdopamineand
norepinephrine.Withrepeateduse,thiscancausetwothingstohappen:
1. Thepersonsstoresoftheseneurotransmitterscanbecomedepleted,sothattheydonthave
highenoughlevelstomaintainanormallevelofmood.Theonlywaytofeelokayagainisto
takemoredrug,sothattheyllreleasewhateverstoreofneurotransmittertheyhave.
2. Thesecondthingthathappensisonthepostsynapticneuron.Whenareceptorisexposedto
highlevelsofitsligand(inthiscase,neurotransmitter),thecelltendstorespondbydown
regulatingthereceptors.Thismeansthatthepostsynapticneuronmayturnoffthegenefor
theproductionofneurotransmitterreceptors,and/ordecreasetheexpressionofthereceptor
onthecellmembrane.Thenetresultisthatthepostsynapticneuronbecomeslesssensitive
totheneurotransmitter.Onceagain,theonlywaytofeelbetteristotakemoredrug,sothat
thereceptorsthatyouhavearefullyoccupied.
3. Thisisthephysicalbasisoftolerancetoadrug.Thecombinationofdepletionof
neurotransmitterwithadecreasedsensitivitytoitalsoexplainswhyapersonwould
experiencewithdrawlsymptomswhenthedrugisnotused.Thenaturallevelsofthese
neurotransmittersaretoolowtokeepthepersoninanormalstate.

E. Thereissomeevidencethatdopamineneurotransmissionneverrecoversinpeoplewithcertain
typesofaddictions.
1. Manyformeraddictsreportthatlifebecomesdullandlacklusteraftertheystopusingdrugs.
Thissuggestspermanentchangestothefunctionofthepleasurecentersintheirbrains
2. Thereisevidencethatdopaminetransportersaredepletedinformermethamphetamineusers,
whichwoulddecreasethereleaseofdopamineinreponsetopleasurablestimuli.

F. Relatedquestionsarewhydopeoplestartusingdrugsinthefirstplace?Andwhydoonlysome
peoplebecomeaddictedtodrugs?
1. Itisthoughtthatmanypeoplewhousedrugsareactuallyselfmedicating.
a. Theymaybesufferingfromdepressionoranxiety,andmaychoosedrugsthathelpthem
copewiththesefeelings.

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 b. Downatthecellularlevel,thismaymeanthattheirstoresofimportantneurotransmitters
likeserotonin,norepinephrineanddopamineareabnormallylow,andtheytakethedrugs
tofeelnormal.
2. However,theveryabnormalitiesthatmakethemseekoutthesedrugsmaymakethemmore
vulnerabletoaddiction,iftheirnervecellsareslowtorecoverfromtheeffectsofdruguse.
3. Wecantakethequestionfurtherandaskwhatcausessomepeopletohavelowlevelsof
theseneurotransmitters?Isitgenesorenvironment?Thereisresearchtosupportimportant
rolesforboth.
a. Addictionsruninfamilies,andthetendencytodevelopaddictionspersistsinchildrenof
addictedbirthparentswhohavebeenadoptedbynonaddictedparents.
b. Psychologicalstressactivatesnorepinephrine,dopamineandserotoninneuralactivity,
anditispossiblethatexposuretopsychologicaltraumaleadstodisordersinthefunction
oftheseneuralpathwaysinthedevelopingbrain.
c. Prenatalstresshasbeenshowntohavelongtermeffectsontheactivityofthe
dopaminergicsystemandondopaminerelatedactivities
4. Itisalsoimportanttonotethatdefinitionsofaddictionanddrugabusearesomewhatcultural.
Theamountofalcoholconsumptionvariesgreatlyfromcountrytocountry.Manydrugsof
abuse,suchascocaineandopiates,areusedinsomeforminothercultureswithoutasmuch
concernaboutaddiction.

G. Howdoyoutreatanaddiction?
1. Ifthepersonappearstohaveasignificantphysicaladdictiontothesubstance,thefirststepis
detox.Thisinvolveshavingthepersonsafelywithdrawfromthedrug,usuallyina
hospitalsetting.Thistypicallytakesafewdaysorafewweeks,dependingonthedrug.
2. Thenextstepisrehabilitation,wherethepersondealswiththepsychologicalaswellasthe
physicalaspectsoftheiraddiction.Thisrequiresaseriouscommitmentonthepartofthe
addictedperson.Ittakesmuchlongersometimesitisalifelongprocess.Rehabilitation
sometimesbeginsinaninstitutionalsetting,butmostoftentakesplacethroughoutpatient
visitstopsychologists,12stepmeetingsandothersupportivegroups.
3. Medicationcanhelpinsomecases.Someexamples:
a. Nicotinepatcheshelpapersonstopsmokingbygivingthemthephysicalpresenceof
nicotine,withoutthehabitual(andhazardous)activityofsmoking.
b. Thedrugmethadonestimulatesthesamereceptorsascommonlyabusedopioidssuchas
heroin,morphineorprescriptionpainkillers.Itbindsmoretightlytotheopioids
receptorsthandothesedrugs,andmaintainsastablelevelofactivationofthese
receptors.Whentakenasprescribed,itdoesnotcauseahigh.
c. Alcoholicsaresometimesgivenadrugcalledantabuse,whichcausesapersontobecome
physicallyilliftheyconsumealcohol.
d. Peoplewithvarioustypesofaddiction(especiallysmoking)alsobenefitfroman
antidepressantcalledBupropion(Wellbutrin),whichblocksreuptakeofboth
norepinephrineanddopamineatthesynapse.Thiskeepsdopamineavailablelonger,
stabilizinglevelsofthisneurotransmitter,andkeepingapersonsmoodstableaswell.

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 Major Neurotransmitters
(just for your information)
Small Molecules Neuropeptides
Acetylcholine Hypothalamic Releasing Hormones
Nitric Oxide Corticotrophic Releasing Hormone
Biogenic Amines Growth Hormone Releasing Hormone
Epinephrine Thyrotrophin Releasing Hormone
Norepineprine Pituitary Peptides
Dopamine endorphins
Serotonin Oxytoxin
Histamine Vasopressin
Amino Acids Adrenocorticotropic Hormone (ACTH)
Glutamate Thyroid Stimulating Hormone (TSH)
Aminobutyric Acid (GABA) Growth Hormone
Glycine Gastrointestinal Peptides
Aspartate Secretin
Homocysteine Substance P
Taurine Insulin
Nucleotides Gastrin
Adenosine Neurotensin
Adenosine triphosphate Somatostatin
Cholecystokinin
Others
Angiotensin
Bradykinin
Neuropeptide Y
Calcitonin

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